This eork will contunue toward its overall objective of elucidating the mechanisms of intestinal infection in cholera and the mode of action of antibacterial and antitoxic immunity. Further study is planned on the mechanisms of invasion by V. cholerae of the mucous gel of the periviller and interviller spaces, as well as the role of anti-somatic antigen antibody in preventing invasion. The behavior of both motile strains and their non-motile variants will be studied in rabbit ileal loops. Further studies will be made of the specific binding of purified cholera toxin to receptors on intestinal mucosal cells and cells of other tissues, as well as the specific inhibition of binding as the primary action of cholera antitoxin as the means of providing protection to the mucosa. Studies will be made of various fragments, subunits and chemically altered cholera toxins for binding properties, immunogenicity, and ability to react with various antitoxins, with the objective of deriving a moiety that will not bind to cell receptors (and is therefore non-toxic) but will be immunogenic in producing neutralizing antitoxin.